Plasma angiopoietin-1, angiopoietin-2 and Tie-2 in breast and prostate cancer: a comparison with VEGF and Flt-1


  • Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine (G. J. Caine, A. D. Blann, G. Y. H. Lip), and Departments of Surgery (P. S. Stonelake) and Urology (P. Ryan), City Hospital, Birmingham, UK.

G. Y. H. Lip, Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham B18 7QH, UK Tel.: +44 121 554 4083; fax: +44 121 507 5080; e-mail:


Background  Angiogenesis is essential for tumour growth and metastasis, and is coordinated by several classes of growth factors mediating their effect through receptors linked, in turn, to tyrosine kinase. These growth factors include angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF), which act through receptors Flt-1 and Tie-2.

Materials and methods  In order to further determine abnormalities in levels of Ang-1, Ang-2, Tie-2, sFlt-1 and VEGF in human cancer (and their interrelationships), these molecules were measured in plasma from 30 patients with breast cancer, 30 patients with prostate cancer and 12 healthy controls per cancer group.

Results  In breast cancer, levels of Ang-1 (P = 0·0005), Ang-2 (P = 0·0173), Tie-2 (P = 0·0001), and VEGF (P = 0·0001) were all significantly raised, and plasma levels of sFlt-1 (P = 0·045) were significantly reduced compared with controls. However, in prostate cancer, only levels of VEGF and Tie-2 were significantly higher (both P= 0·001). There were no significant differences between levels of any molecule between the two groups of cancer. The only difference between the healthy control groups was lower Ang-1 in the women compared with men. Significant correlations were found between levels of Ang-1 and Tie-2 both in breast (r = 0·498, P= 0·005) and prostate cancer (r = 0·643, P= < 0·001). Angiopoietin-1 was also positively correlated with Ang-2 in both breast (r = 0·422, P= 0·02) and prostate cancer (r = 0·543, P= 0·002).

Conclusions  Abnormal levels of Ang-1, Ang-2 and their receptor, Tie-2, are present in breast and prostate cancer, and their interrelationships may be important in the pathophysiology of these conditions.